Many disorders of the human central nervous system are associated with abnormal patterns of physiologic activity in brain circuitry. One group of diseases involves abnormalities in a family of parallel circuits that control both motor and non-motor functions. These circuits belong to a group of structures known as the basal ganglia. It is recognized from research studies of animals and clinical studies in humans with brain injuries or diseases that rates and patterns of electrophysiological activity are abnormal in many basal ganglia circuits. Notable examples of human conditions involving these circuits include Parkinson's disease, various forms of tremor, and disorders involving muscle tone (dystonia). Other syndromes that do not involve movement also may have basal ganglia involvement (e.g. obsessive compulsive disorder, pain, etc.) Patients suffering from these conditions present with one or more of variety of symptoms of motor deficiency including tremor, muscle rididity, loss or impairment of voluntary muscle activity (akinesia or dyskinesia), and gait irregularity. They may also present with non-motor symptoms (depression, anxiety, OCD, etc.).
Debilitating movement disorders have been treated by non-reversible surgical ablation of affected brain circuits, for example by procedures such as thalamotomy or pallidotomy. Deep brain stimulation (DBS) therapy is an attractive alternative to such permanent surgeries, providing the distinct advantages of reversibility and adjustability of treatment over time. DBS is a treatment method that aims to change the rates and patterns of activity of brain cells by implanting a brain stimulator (i.e., an electrode, also known as a lead) into a target region in the brain known to be associated with movement, including the thalamus, subthalamic nucleus (STN), globus pallidus, internal capsule, and nucleus accumbens.
Electrical stimulation by DBS of a particular target region of the brain, in some cases bilaterally (i.e., using an electrode on each side of the brain to stimulate paired target regions located on each side of the brain) has been successfully used to treat symptoms of several movement disorders. For example, it has been reported in several studies that targeting of the STN is effective to alleviate symptoms of Parkinson's disease. Other areas of the brain that have been successfully targeted for this disease include the globus pallidus internus (GPi) and the ventro-lateral thalamus (VIM/VOP). Clinical results of DBS therapy for treatment of several movement disorders, including Parkinson's disease and essential tremor, have been recently reviewed in Tronnier et al., Minim. Invas. Neurosurg. 45:91-96, 2002 and in Pollack et al., Movement Disorders 17:575-583, 2002).
Despite documented successes of DBS for some forms of Parkinson's disease and essential tremor (Benabid, A. L., et al., Stereotact Funct Neurosurg, 1994. 62(1-4):76-84; Benabid, A. L., et al., J Neurol, 2001. 248 Supply. 3: III37-47), many movement disorders are unresponsive or only partially benefited by current DBS procedures. Additionally, the success of DBS procedures can diminish over time. Thalamic lesioning (Kim, M. C., et al., J Neurol Neurosurg Psychiatry, 2002. 73(4):453-5; Deuschl, G., et al., Ann Neurol, 1999. 46(1):126-8; Krauss, J. K., et al., J Neurosurg, 1994. 80(5):810-9) and thalamic DBS (Pahwa, R., et al., Mov Disord, 2002. 17(2):404-7; Samadani, U., et al., J Neurosurg, 2003. 98(4): 888-90) have both failed to consistently alleviate tremors due to structural and post-traumatic lesions affecting the cerebellothalamic and dopaminergic systems. Surgical treatment of a similar tremor associated with multiple sclerosis has also been relatively ineffective (Berk, C., et al., J Neurosurg, 2002. 97(4):815-20; Hooper, J., et al., Br J Neurosurg, 2002. 16(2):102-9; Schulder, M., et al., Stereotact Funct Neurosurg, 1999. 72(2-4): p. 196-201). Thus, there is an ongoing need for improved therapy for these conditions.
In recent years there has been a growing appreciation that DBS methods are applicable to a much wider range of brain-associated disorders than previously appreciated. Accordingly, there is a need for improved DBS therapies for treating a variety of conditions involving abnormal physiology of the brain.